Acetaminophen And Codeine and Lofexidine: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jun 30, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Acetaminophen And Codeine
Lofexidine
No brand names on record
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Both of these medicines can slow down your brain and body. Your acetaminophen with codeine is a pain reliever that contains an opioid, and opioids can make you drowsy and slow your breathing. Lofexidine, which helps with opioid withdrawal symptoms, can also cause sleepiness, dizziness, and lower blood pressure.
When you take them together, these calming effects can add up. You may feel more sleepy or lightheaded than usual. Please be careful about driving or using machinery until you know how you feel. The good news is your care team can manage this by watching you closely and adjusting things as needed. Talk with your pharmacist or doctor if you feel very drowsy.
Effect: Additive CNS depression when acetaminophen/codeine is combined with lofexidine.
- Mechanism: Pharmacodynamic (additive), not pharmacokinetic. Codeine (an opioid; also a CYP2D6 prodrug for morphine, though that is not the driver here) produces sedation and respiratory depression; lofexidine, a central alpha-2 agonist, adds sedation, dizziness, and hypotension/bradycardia.
- Direction: Increased sedation, psychomotor impairment, and potential respiratory/hemodynamic depression.
- Onset: Unspecified. Evidence: Theoretical. Severity: Major.
- Management: Counsel against driving/operating machinery; monitor sedation, blood pressure, heart rate, and respiratory status. Doses may be individualized by the care team.
What happens
Increased risk of CNS depressant effects
Interaction Deep Dive
Combining lofexidine with this drug can lead to heightened CNS depressant activity. Caution is advised for patients, who should refrain from driving or handling heavy machinery1.
Why it happens (mechanism)
Additive CNS depression
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination is used cautiously, and your care team can manage it.
- Avoid or use caution with driving or operating heavy machinery until you know how the combination affects you.
- Watch for excessive drowsiness, dizziness, confusion, slowed breathing, or feeling faint when standing.
- Your team may monitor you more closely, and either dose may be adjusted and individualized for you.
- Tell your pharmacist or prescriber about any new sedatives, sleep aids, or alcohol, since these add to the effect.
Management is individual — confirm any change with your pharmacist or prescriber.
Common questions
Can I take Acetaminophen And Codeine and Lofexidine together?
Taking acetaminophen with codeine alongside lofexidine can add up to more drowsiness, dizziness, and slowed breathing, so avoid driving until you know how you feel and let your care team monitor and adjust as needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Acetaminophen And Codeine and Lofexidine interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Acetaminophen And Codeine and Lofexidine interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination is used cautiously, and your care team can manage it. Avoid or use caution with driving or operating heavy machinery until you know how the combination affects you. Watch for excessive drowsiness, dizziness, confusion, slowed breathing, or feeling faint when standing. Your team may monitor you mor… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Acetaminophen And Codeine or Lofexidine need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (1)
- Product Information: LUCEMYRA(TM) oral tablets, lofexidine oral tablets. US WorldMeds LLC (per FDA), Louisville, KY, 2018. DailyMed
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